Process for production of thioalkylamine derivatives

ABSTRACT

The present invention relates to a thioalkylamine derivative represented by general formula (I); and a process for production thereof:                    
     wherein each of R 1  and R 2  is H, (C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (substituted) phenyl, (substituted) phenyl(C 1 -C 4 )alkyl, or the like; each of R 3  and R 4  is H or a (C 1 -C 4 )alkyl group; each of R 5  and R 6  is H, (C 1 -C 4 )alkyl, a (substituted) phenyl group or a (substituted) phenyl(C 1 -C 4 )alkyl group; alternatively each of R 1  and R 2 , R 1  and R 3  or R 5 , R 3  and R 4 , R 3  and R 5  or R 5  and R 6  may together form lower alkylene; and R is (C 1 -C 12 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (substituted) phenyl, (substituted) phenyl(C 1 -C 4 )alkyl, a naphthyl group, a (substituted) aromatic heterocyclic, or the like.

This application is a 371 of PCT/JP00/06673 filed Sep. 27, 2000, nowSer. No. WO 01/23350.

TECHNICAL FIELD

The present invention relates to thioalkylamine derivatives representedby general formula (I) which are useful as intermediates of medicines,agrochemicals, chemical products, etc., and a process for production ofthe derivatives.

BACKGROUND ART

Thioalkylamine derivatives are useful as intermediates for synthesis ofagrochemicals, medicines, chemical products, etc. or starting materialsfor them. When used in agrochemicals, the derivatives are usefulcompounds as, for example, starting compounds for the agricultural andhorticultural insecticide disclosed in Japanese Patent Application No.11-338715 filed by the same applicant as the present applicant.

Thioalkylamines can be classified into thiols and sulfides according tochemical structure. As a process for producing any of the thiols and thesulfides, the following processes have been reported.

(1) A process in which a thiol is produced by hydrolyzing a thiazolineor thiazolidinone derivative (for example, J. Med. Chem., 1965, 8, 762;JP-A-59-231064; Bull. Soc. Chim. Fr. 1967, 3637; and Z. Naturforsch., B:Chem. Sci. 1987, 42, 348). (2) A process in which a sulfide is producedby reacting an oxazoline or oxazolidinone derivative with a thiol (forexample, J. Org. Chem., 1992, 57,6257; and J. Med. Chem., 1984, 27,1354). (3) A process in which a sulfide or a thiol is produced byreacting an aziridine with a sulfur compound such as a mercaptan (forexample, Tetrahedron, 1992, 48, 2359; J. Am. Chem. Soc., 1986,108,.3811; Inorg. Chem., 1984, 23, 3404; and Tetrahedron Lett., 1983,24, 2131). (4) A process in which a sulfide is produced by hydrolyzingan amide obtained by reacting an amino alcohol with a mercaptan in acarboxylic acid (for example, Neth. Appl. 6, 404, 644). (5) A process inwhich a thiol is produced by reacting an amino alcohol sulfate esterwith ammonium hydrogensulfide (for example, Journal of Chemical Societyof Japan, 1979, 149). (6) A process in which a thioalkyl alcohol isconverted to a thioalkylamine by Ritter reaction and hydrolysis (forexample, Ger. Offen. 2,045,905).

A desired compound in the present invention is a sulfide as athioalkylamine. Therefore, of the above prior arts, the productionprocesses (2), (3), (4) and (6) are closely concerned with the desiredcompound. However, the process (2) involves, for example, the followingproblem: it requires a hydrolysis step because the product is obtainedas an amide, and the reaction does not take place if a substituent suchas an alkyl group is present in the oxazolidine ring of the startingcompound. This process is also disadvantageous in that only an aromaticsulfide can be produced owing to the acidity of a mercapto group. Theprocess (3) is not suitable for industrial adoption from the viewpointof safety and facilities because the aziridine whose toxicity tends toaffect the health of production workers is used after its production andisolation. The process (4) is disadvantageous, for example, in that theproduct is limited to a thiol because the reaction is carried out withheating under pressure for a long period of time. Moreover, this processis disadvantageous, for example, in that like the process (2), itrequires hydrolysis because the product is obtained as an amide. Theprocess (6) is disadvantageous, for example, in that an excess ofprussic acid is used which is very toxic and requires great care inhandling and after-treatment, or that the hydrolysis is not easy when aneasily handleable nitrile is used.

Although the processes (1) and (5) are production processes of a thioland are not directly concerned with a process for producing a sulfideintended according to the present invention, they involve the followingproblems. That is, the process (1) is industrially disadvantageous fromthe viewpoint of the number of steps and yield because the thiazoline orthiazolidinone derivative should be produced. The process (5) isindustrially disadvantageous in that it entails high cost in view offacilities and production efficiency because the reaction is carried outin a sealed tube for a long period of time.

The present invention avoids, for example, the following variousproblems in prior arts: a reaction is carried out at a high temperatureand a high pressure for a long period of time; an additional step suchas hydrolysis is needed; there are various restrictions on introduciblesubstituents; and the toxicity of a starting material used and the likeis so high that safety and facilities required for handling andafter-treatment of the staring material and the like cost a great deal.Thus, the present invention provides a production process which issimple and short, can be generally adopted, can be safely practiced, andis economically advantageous.

DISCLOSURE OF THE INVENTION

In order to solve the above problems and develop a novel process forproducing a thioalkylamine, the present inventors earnestly investigatedand consequently found that the above object can be achieved byproducing a sulfate ester represented by general formula (III) by thereaction of an amino alcohol represented by general formula (II) withsulfuric acid, and reacting the sulfate ester with a mercaptan underbasic conditions, whereby the present invention has been accomplished.

The present invention relates to a thioalkylamine derivative representedby general formula (I):

wherein each of R₁ and R₂, which may be the same or different, is ahydrogen atom; a (C₁-C₄)alkyl group; a (C₃-C₈)cycloalkyl group; a(C₃-C₈)cycloalkyl(C₁-C₄)alkyl group; a hydroxy-(C₁-C₄)alkyl group; aphenyl group; a substituted phenyl group having 1 to 5 substituentswhich may be the same or different and each of the substituents isselected from a halogen atom, a cyano group, a nitro group, a(C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a (C₃-C₈)cycloalkyl group,a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthiogroup, a halo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, a (C₁-C₄)alkylsulfonyl group, ahalo(C₁-C₄)alkylsulfonyl group, a carboxyl group, a(C₁-C₄)alkoxycarbonyl group, a (C₁-C₄)alkoxy(C₁-C₄)alkyl group,R₇—C(═O)— (wherein R₇ is a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group,a phenyl group or a phenoxy group), an amino group, and a substitutedamino group having one or two substituents which may be the same ordifferent and are selected from (C₁-C₄)alkyl groups; a substitutedphenyl group having as the substituent a (C₃-C₄)alkylene group or a(C₁-C₂)alkylenedioxy group, which forms a ring together with a pair ofadjacent carbon atoms in the benzene ring; a phenyl(C₁-C₄)alkyl group;or a substituted phenyl(C₁-C₄)alkyl group having on the ring 1 to 5substituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a cyano group, a nitrogroup, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; R₁ andR₂ may form a (C₂-C₅)alkylene group by binding to each other; R₁ and R₃or R₅ may form a (C₃-C₅)alkylene group by binding to each other,

each of R₃ and R₄, which may be the same or different, is a hydrogenatom or a (C₁-C₄)alkyl group; R₃ and R₄ may form a (C₄-C₆)alkylene groupby binding to each other; R₃ and R₅ may form a (C₂-C₄)alkylene group bybinding to each other,

each of R₅ and R₆, which may be the same or different, is a hydrogenatom; a (C₁-C₄)alkyl group; a phenyl group; a substituted phenyl grouphaving 1 to 5 substituents which may be the same or different and eachof the substituents is selected from a halogen atom, a cyano group, anitro group, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; aphenyl(C₁-C₄)alkyl group; or a substituted phenyl(C₁-C₄)alkyl grouphaving on the ring 1 to 5 substituents which may be the same ordifferent and each of the substituents is selected from a halogen atom,a cyano group, a nitro group, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkylgroup, a (C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, ahalo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthio group, ahalo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, a (C₁-C₄)alkylsulfonyl group and ahalo(C₁-C₄)alkylsulfonyl group; R₅ and R₆ may form a (C₄-C₆)alkylenegroup by binding to each other, and

R is a (C₁-C₁₂)alkyl group; a (C₃-C₈)cycloalkyl group; a(C₃-C₈)cycloalkyl(C₁-C₄)alkyl group; a phenyl group; a substitutedphenyl group having 1 to 5 substituents which may be the same ordifferent and each of the substituents is selected from a halogen atom,a (C₁-C₆)alkyl group, a halo(C₁-C₃)alkyl group, a (C₃-C₈)cycloalkylgroup, a (C₁-C₄)alkoxy group and a halo(C₁-C₄)alkoxy group; aphenyl(C₁-C₄)alkyl group; a substituted phenyl(C₁-C₄)alkyl group havingon the ring 1 to 5 substituents which may be the same or different andeach of the substituents is selected from a halogen atom and a(C₁-C₄)alkyl group; a naphthyl group; an aromatic heterocyclic group; ora substituted aromatic heterocyclic group having one or moresubstituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a (C₁-C₄)alkyl group, a(C₁-C₄)alkoxy group, a phenyl group, and a substituted phenyl grouphaving 1 to 5 substituents which may be the same or different and eachof the substituents is selected from a halogen atom and a (C₁-C₄)alkylgroup,

provided that:

(1) when R₁, R₂, R₃, R₄, R₅ and R₆ are hydrogen atoms at the same time,then R is not a (C₁-C₆)alkyl group, phenyl group and aromaticheterocyclic group of 2-furyl group, 2-thienyl group, 2-thiazolyl group,2-imidazolyl group, 2-pyridyl group and 2-pyrimidinyl group.

(2) when R₁, R₂, R₃, R₄ and R₆ are hydrogen atoms at the same time andR₅ is a (C₁-C₄)alkyl group or a phenyl group, then R is not a(C₁-C₄)alkyl group, phenyl group and aromatic heterocyclic group ofpyridyl group and pyrimidinyl group.

(3) when R₁, R₂, R₃ and R₄ are hydrogen atoms at the same time and eachof R₅ and R₆ is a (C₁-C₄)alkyl group or a phenyl group, then R is not a(C₁-C₅)alkyl group, phenyl group and aromatic heterocyclic group oftriazolyl group, tetrazolyl group, 1,2,3-thiadiazolyl group, pyridylgroup, 2-pyrimidinyl group and pyrazinyl group,

(4) when R₂, R₃, R₄, R₅ and R₆ are hydrogen atoms at the same time and Ris a phenyl group, then R₁ is not a (C₁-C₄)alkyl group and phenyl group,

(5) when R₂, R₃, R₄, R₅ and R₆ are hydrogen atoms at the same time andR₁ is a methyl group, then R is not a methyl group and aromaticheterocyclic group of 2-benzothiazolyl group,

(6) when R₂, R₃, R₄ and R₆ are hydrogen atoms at the same time, R₁ is amethyl group and R is a methyl group, then R₅ is not a (C₁-C₃)alkylgroup and phenyl group,

(7) when R₂, R₃, R₄, R₅ and R₆ are hydrogen atoms at the same time andR₁ is an ethyl group, then R is not an aromatic heterocyclic group of2-indolyl group,

(8) when R₂, R₃, R₄ and R₅ are hydrogen atoms at the same time, R₆ is aphenyl group and R₁ is a methyl group, then R is not a methyl group andt-butyl group,

(9) when R₂, R₃, R₄ and R₅ are hydrogen atoms at the same time, R₆ is aphenyl group and R₁ is a propyl group, then R is not a methyl group andphenyl group,

(10) when R₂, R₃ and R₄ are hydrogen atoms at the same time, each of R₅and R₆ is a methyl group, a propyl group or a phenyl group and R₁ is amethyl group, then R is not a methyl group, t-butyl group and phenylgroup,

(11) when R₂, R₃ and R₄ are hydrogen atoms at the same time, R₅ and R₆are methyl groups at the same time and R₁ is a propyl group, then R isnot an ethyl group and phenyl group,

(12) when R₂, R₃, R₄ and R₅ are hydrogen atoms at the same time, R₁ is aphenyl group and R is a methyl group or a phenyl group, then R₆ is not amethyl group, n-propyl group and phenyl group,

(13) when R₂, R₃, R₄ and R₅ are hydrogen atoms at the same time, R₁ is aphenyl group and R is a butyl group, then R₆ is not a hydrogen atom andmethyl group,

(14) when R₂, R₃ and R₄ are hydrogen atoms at the same time, R₅ and R₆are methyl groups at the same time and R₁ is a phenyl group, then R isnot a methyl group and phenyl group,

(15) when R₁, R₂, R₄, R₅ and R₆ are hydrogen atoms at the same time andR₃ is a methyl group, then R is not a methyl group and phenyl group,

(16) when R₁, R₂ and R₄ are hydrogen atoms at the same time, R₃ is a(C₁-C₄)alkyl group and each of R₅ and R₆ is a methyl group, an ethylgroup or a phenyl group, then R is not a (C₁-C₃)alkyl group and phenylgroup,

(17) when R₃, R₄, R₅ and R₆ are hydrogen atoms at the same time and R₁and R₂ are methyl groups at the same time, then R is not a methyl group,ethyl group and phenyl group,

(18) when R₃, R₄, R₅ and R₆ are hydrogen atoms at the same time and R₁and R₂ are n-propyl groups at the same time, then R is not a methylgroup,

(19) when R₃, R₄, R₅ and R₆ are hydrogen atoms at the same time, R₁ isan ethyl group and R₂ is an n-butyl group, then R is not an aromaticheterocyclic group of 2-thienyl group,

(20) when R₃, R₄ and R₆ are hydrogen atoms at the same time, R₁ and R₂are methyl groups at the same time and R₅ is a phenyl group, then R isnot a phenyl group,

(21) when R₃ and R₄ are hydrogen atoms at the same time and R₁, R₂, R₅and R₆ are methyl groups at the same time, then R is not a methyl group,

(22) when R₁, R₂, R₅ and R₆ are hydrogen atoms at the same time and R₃and R₄ are methyl groups at the same time, then R is not a methyl group,

(23) when R₁, R₂ and R₆ are hydrogen atoms at the same time, R₃ and R₄are methyl groups at the same time and R₅ is a t-butyl group, then R isnot a phenyl group,

(24) when R₁ and R₂ are hydrogen atoms at the same time and R₃, R₄, R₅and R₆ are methyl groups at the same time, then R is not a methyl group,

(25) when R₂, R₄, R₅ and R₆ are hydrogen atoms at the same time, R₁ is amethyl group, an ethyl group or a phenyl group and R₃ is a methyl group,then R is not a methyl group and phenyl group,

(26) when R₂, R₄, R₅ and R₆ are hydrogen atoms at the same time, R₁ is a(C₁-C₄)alkyl group and R₃ is an n-butyl group, then R is not a methylgroup,

(27) when R₂, R₄ and R₆ are hydrogen atoms at the same time, R₁ is anethyl group and R₃ and Rare methyl groups at the same time, then R₅ isnot a methyl group and ethyl group,

(28) when R₂ and R₄ are hydrogen atoms at the same time, each of R₁ andR₆ is a methyl group or an ethyl group and R₃ and R₅ are methyl groupsat the same time, then R is not a methyl group and phenyl group, and

(29) when R₁ is an isopropyl group, R₂, R₅ and R₆ are hydrogen atoms atthe same time and R₃ and R₄ are methyl groups at the same time, then Ris not a methyl group. Furthermore, the present invention relates to anovel process for producing a thioalkylamine derivative represented bygeneral formula (I):

(wherein R₁, R₂, R₃, R₄, R₅, R₆ and R are as defined below) andincluding well-known thioalkylamine derivatives, which is characterizedby reacting sulfuric acid with an amino alcohol represented by generalformula (II):

(wherein each of R₁ and R₂, which may be the same or different, is ahydrogen atom; a (C₁-C₄)alkyl group; a (C₃-C₈)cycloalkyl group; a(C₃-C₈)cycloalkyl(C₁-C₄)alkyl group; a hydroxy(C₁-C₄)alkyl group; aphenyl group; a substituted phenyl group having 1 to 5 substituentswhich may be the same or different and each of the substituents isselected from a halogen atom, a cyano group, a nitro group, a(C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a (C₃-C₈)cycloalkyl group,a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthiogroup, a halo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, a (C₁-C₄)alkylsulfonyl group, ahalo(C₁-C₄)alkylsulfonyl group, a carboxyl group, a(C₁-C₄)alkoxycarbonyl group, a (C₁-C₄)alkoxy(C₁-C₄)alkyl group,R₇—C(═O)— (wherein R₇ is a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group,a phenyl group or a phenoxy group), an amino group, and a substitutedamino group having one or two substituents which may be the same ordifferent and are selected from (C₁-C₄)alkyl groups; a substitutedphenyl group having as the substituent a (C₃-C₄)alkylene group or a(C₁-C₂)alkylenedioxy group, which forms a ring together with a pair ofadjacent carbon atoms in the benzene ring; a phenyl(C₁-C₄)alkyl group;or a substituted phenyl(C₁-C₄)alkyl group having on the ring 1 to 5substituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a cyano group, a nitrogroup, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; R₁ andR₂ may form a (C₂-C₄)alkylene group by binding to each other; R₁ and R₃or R₅ may form a (C₃-C₅)alkylene group by binding to each other,

each of R₃ and R₄, which may be the same or different, is a hydrogenatom or a (C₁-C₄)alkyl group; R₃ and R₄ may form a (C₄-C₆)alkylene groupby binding to each other; R₃ and R₅ may form a (C₂-C₄)alkylene group bybinding to each other,

each of R₅ and R₆, which may be the same or different, is a hydrogenatom; a (C₁-C₄)alkyl group; a phenyl group; a substituted phenyl grouphaving 1 to 5 substituents which may be the same or different and eachof the substituents is selected from a halogen atom, a cyano group, anitro group, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; aphenyl(C₁-C₄)alkyl group; or a substituted phenyl(C₁-C₄)alkyl grouphaving on the ring 1 to 5 substituents which may be the same ordifferent and each of the substituents is selected from a halogen atom,a cyano group, a nitro group, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkylgroup, a (C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, ahalo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthio group, ahalo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, a (C₁-C₄)alkylsulfonyl group and ahalo(C₁-C₄)alkylsulfonyl group; and R₅ and R₆ may form a (C₄-C₆)alkylenegroup by binding to each other) to obtain a sulfate ester represented bygeneral formula (III):

(wherein R₁, R₂, R₃, R₄, R₅ and R₆ are as defined above), and reactingthe sulfate ester, after or without isolation, with a mercaptanrepresented by general formula (IV):

RSM  (IV)

(wherein R is a (C₁-C₁₂)alkyl group; a (C₃-C₈)cycloalkyl group; a(C₃-C₈)cycloalkyl(C₁-C₄)alkyl group; a phenyl group; a substitutedphenyl group having 1 to 5 substituents which may be the same ordifferent and each of the substituents is selected from a halogen atom,a (C₁-C₆)alkyl group, a halo(C₁-C₃)alkyl group, a (C₃-C,)cycloalkylgroup, a (C₁-C₄)alkoxy group and a halo(C₁-C₄)alkoxy group; aphenyl(C₁-C₄)alkyl group; a substituted phenyl(C₁-C₄)alkyl group havingon the ring 1 to 5 substituents which may be the same or different andeach of the substituents is selected from a halogen atom and a(C₁-C₄)alkyl group; a naphthyl group; an aromatic heterocyclic group; ora substituted aromatic heterocyclic group having one or moresubstituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a (C₁-C₄)alkyl group, a(C₁-C₄)alkoxy group, a phenyl group and a substituted phenyl grouphaving 1 to 5 substituents which may be the same or different and eachof the substituents is selected from a halogen atom and a (C₁-C₄)alkylgroup, and M is a hydrogen atom, an ammonium group or an alkali metalatom).

By the production process of the present invention, a thioalkylamine canbe produced safely without directly handling a very toxic reagent,intermediate or the like. Moreover, the production process permitsindustrially advantageous production of said thioalkylamine withoutusing a special reactor or the like.

MODE FOR CARRYING OUT THE INVENTION

Examples of the substituents in the present invention are given below.In the abbreviated representation of the chemical formulas in thepresent invention, “i-” is a prefix for “iso”, “s-” is a prefix for“secondary”, and “t-” is a prefix for “tertiary”.

In the definition of the substituents of the thioalkylamine derivativerepresented by general formula (I) of the present invention, the term“halogen atom” means a chlorine atom, a bromine atom, an iodine atom ora fluorine atom. The term “(C₁-C₄)alkyl” or “(C₁-C₆)alkyl,” means alinear or branched alkyl group of 1 to 4 carbon atoms or 1 to 6 carbonatoms, respectively, such as methyl, ethyl, n-propyl, i-propyl, n-butyl,i-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl or the like. The term“halo(C₁-C₄)alkyl” or “halo(C₁-C₆)alkyl” means a substituted linear orbranched alkyl group of 1 to 4 carbon atoms or 1 to 6 carbon atoms,respectively, having as the substituent(s) one or more halogen atomswhich may be the same or different. The term “(C₃-C₆)alkylene” means alinear or branched alkylene group of 3 to 6 carbon atoms, such aspropylene, trimethylene, dimethylmethylene, tetramethylene,methyltrimethylene, dimethylethylene or the like.

The aromatic heterocyclic group includes, for example, furan, thiophene,pyrrole, oxazole, oxazoline, isoxazole, thiazole, isothiazole,imidazole, pyrazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole,1,2,4-thiadiazole, 1,3,4-thiadiazole, 1,2,3-thiadiazole,1,2,5-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine,pyrimidine, pyridazine, pyrazine and triazine. In any of these groups,one or more nitrogen atoms in the molecule may be oxidized. In addition,benzo derivatives of these groups may also be used. The “benzoderivatives” include, for example, benzofuran, isobenzofuran,1-benzothiophene, 2-benzothiophene, indole, isoindole,1,2-benzothiazole, 1,3-benzothiazole, 2,1- benzothiazole, indazole,benzimidazole, quinoline, isoquinoline, quinazoline, quinoxaline,cinnoline, phthalazine, 1,2,3-benzothiadiazole, benzotriazole,benzoxazine, benzothiazine, benzopyridazine, 1-oxo-4-azanaphthalene and1-thia-4-azanaphthalene. The substitution position(s) in the benzoderivatives is not particularly limited.

The thioalkylamine derivatives of general formula (I) of the presentinvention can be produced, for example, by the production processschematically shown below:

wherein R₁, R₂, R₃, R₄, R₅, R₆ and R are as defined above.

The thioalkylamine of general formula (I) can be produced by reacting anamino alcohol of general formula (II) with sulfuric acid in the presenceof an inert solvent to produce a sulfate ester of general formula (III),and reacting the sulfate ester with a mercaptan of general formula (IV)in the presence of a base and an inert solvent after or withoutisolating the sulfate ester.

1. General Formula (II)→General Formula (III)

In the case of this reaction, the desired compound can be produced bydistilling off the water from a mixed aqueous solution of the aminoalcohol of general formula (II) and sulfuric acid. The desired compoundcan be produced by the process described, for example, in OrganicSyntheses Collective Volume 3, 148 and J. Am. Chem. Soc., 1959, 81,4689.

As the amino alcohol as staring material in the reaction, there can beused, for example, ethanolamine, 2-amino-1-propanol,2-amino-2-methyl-1-propanol, 2-amino-1-butanol, 2-amino-1-pentanol,2-amino-3-methyl-1-butanol, 2-amino-1-hexanol, isoleucinol, leucinol and1-amino-1-cyclopentanemethanol.

In the reaction, an azeotropic dehydrating solvent is preferably used inorder to remove continuously the water produced in the reaction system.As the azeotropic dehydrating solvent, there can be used, for example,aromatic hydrocarbons such as benzene, toluene, xylene, etc.;halogenated hydrocarbons such as chloroform, dichloroethane,trichloroethane, dichloropropane, trichloroethylene,tetrachloroethylene, fluorobenzene, chlorobenzene, dichlorobenzene,etc.; nitrated hydrocarbons such as nitromethane, nitroethane,nitropropane, etc.; nitrile type hydrocarbons such as acetonitrile,propionitrile, butyronitrile, etc.; polyether type hydrocarbons such asdiglyme, propylene glycol dimethyl ether, etc.; and carbonic acid esterssuch as diethyl carbonate, etc.

The amount of sulfuric acid used may be 1 equivalent or more perequivalent of the amino alcohol of general formula (II). The reactiontemperature may be the boiling point of the inert solvent used. When anazeotropic dehydrating solvent is used, the reaction temperature may beany temperature so long as it permits azeotropic dehydration. Althoughthe reaction time is varied depending on the scale of reaction, thereaction may be carried out in the range of 1 to 24 hours, preferably 1to 10 hours.

The sulfate ester of general formula (III) may be isolated and purifiedif necessary, or it may be used as it is in the subsequent step withoutisolation and purification.

2. General Formula (III)→General Formula (I)

As the mercaptan of general formula (IV) used in this reaction, therecan be used, for example, methylmercaptan, ethylmercaptan,propylmercaptan, isopropylmercaptan, butylmercaptan, hexylmercaptan,cyclohexylmercaptan, octylmercaptan, decylmercaptan, dodecylmercaptan,thiophenol, thiocresol, ethylthiophenol, isopropylthiophenol,t-butylthiophenol, dimethylthiophenol, fluorothiophenol,chlorothiophenol, bromothiophenol, dichlorobenzenethiol,methoxybenzenethiol, benzylmercaptan, chlorobenzylmercaptan,t-butylbenzylmercaptan, naphthalenethiol, mercaptopyridine,2-mercaptopyridine N-oxide, mercaptopyrimidine,dimethylmercaptopyrimidine, dimethoxymercaptopyrimidine,methylfuranthiol, furfurylmercaptan, mercaptoimidazole,2-mercapto-1-methylimidazole, 1,2,4-triazole-3-thiol,4-methyl-1,2,4-triazole-3-thiol, 5-methyl-1,3,4-thiadiazole-2-thiol,4-methyl-1,2,3-thiadiazole-5-thiol and4-t-butyl-1,2,3-thiadiazole-5-thiol. There can also be used salts ofthese compounds, such as alkali metal salts (e.g. sodium salts,potassium salts and lithium salts), ammonium salts, etc. As to theamount of the mercaptan used, the reaction may be carried out bychoosing the amount in the range of 1 to 10 equivalents, preferably 1 to2 equivalents, per equivalent of the sulfate ester of general formula(III).

As the base, there can be used inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, etc. Theamount of the base used ranges from 1 to 5 equivalents, preferably 1 to3 equivalents, per equivalent of the sulfate ester of general formula(III).

As the inert solvent, there can be used, for example, either water or amixed solvent of water and an organic solvent. As the organic solvent,there can be used, for example, alcohols such as methanol, ethanol,propanol, isopropanol, etc.; aromatic hydrocarbons such as benzene,toluene, xylene, etc.; halogenated hydrocarbons such as chloroform,dichloroethane, trichloroethane, dichloropropane, trichloroethylene,tetrachloroethylene, fluorobenzene, chlorobenzene, dichlorobenzene,etc.; nitrated hydrocarbons such as nitromethane, nitroethane,nitropropane, etc.; nitrile type hydrocarbons such as acetonitrile,propionitrile, butyronitrile, etc.; polyether type hydrocarbons such asdiglyme, etc.; and carbonic acid esters such as diethyl carbonate, etc.The alcohols such as methanol, ethanol, etc. may be used singly or as amixture of two or more thereof.

The reaction temperature is 50 to 150° C., preferably 65 to 100° C.Although varied depending on the scale of reaction, the reaction timeranges from several minutes to 24 hours, preferably from 1 to 10 hours.

After completion of the reaction, the desired compound is isolated fromthe reaction system containing the desired compound by a conventionalmethod, and if necessary, purified, whereby the thioalkylaminederivative of general formula (I) can be produced.

When the reactions 1 and 2 are carried out in succession, the reaction 2may be carried out by adding water, the base and the mercaptan to thereaction system without isolating the sulfate ester. As to the amount ofthe base used, when sulfuric acid is used in an amount of more than 1equivalent, the amount of the base should be increased by an amountcorresponding to the surplus sulfuric acid. When a mixed solvent ofwater or an alcohol and an organic solvent is used, the mixing ratio maybe properly chosen so that the amount of water or the alcohol may besufficient to dissolve the sulfate ester and that when a solid mercaptanis used, the amount of the organic solvent is sufficient to dissolvethis mercaptan. When the mercaptan is liquid, the reaction 2 can becarried out without using an organic solvent, though it is preferable touse an organic solvent properly when a mercaptan having a low boilingpoint is used.

EXAMPLES

Typical examples and reference examples of the present invention aredescribed below, but they should not be construed as limiting the scopeof the invention.

Example 1

Production of N-Isopropyl-2-methylthioethylamine

1-1. Production of 2-Isopropylaminoethyl Hydrogensulfate

In a 50-ml three-necked flask, 1.01 g (10 mmol) of sulfuric acid (97%)was diluted with 1 g of water, and the resulting dilution wasice-cooled. A mixture of 1.03 g (10 mmol) of 2-isopropylaminoethanol and1 g of water was slowly dropped into the cooled dilution. Aftercompletion of the dropping, the resulting mixture was warmed to roomtemperature and 10 ml of toluene was added thereto. The mixture thusobtained was dehydrated by heating with vigorous stirring afterattaching a Dean-Stark trap to the flask. The mixture was heated andstirred for 4 hours until a theoretical amount of water was removed.Then, the reaction was continued for another 1 hour. After a largeportion of the toluene was removed by decantation, the residual toluenewas distilled off under reduced pressure to obtain a crude product of2-isopropylaminoethyl hydrogensulfate, the desired compound,quantitatively.

¹H-NMR (δ value, ppm/DMSO-d₆); 1.20 (d, 6H), 3.15 (br, 2H), 3.30 (br,1H), 4.00 (br, 2H), 8.39 (br, 2H).

The following compounds were obtained in the same manner as above:

2-Phenylaminoethyl Hydrogensulfate

¹H-NMR (δ value, ppm/DMSO-d₆); 3.50 (br, 2H), 3.97 (br, 2H), 7.20-7.55(br, 7H).

2-Amino-2-methylpropyl Hydrogensulfate

¹H-NMR (δ value, ppm/DMSO-d₆); 1.20 (s, 6H), 3.58 (br, 2H), 3.72 (s,2H), 7.81 (br, 3H).

1-2. Production of N-Isopropyl-2-methylthioethylamine

In a mixed solvent of 5 ml of water and 5 ml of ethanol was suspended0.69 g (5 mmol) of potassium carbonate, followed by adding thereto 0.92g (5 mmol) of 2-isopropylaminoethyl hydrogensulfate and 2.8 g (6 mmol)of methylmercaptan sodium salt (15% aqueous solution), and the resultingmixture was gently refluxed for 8 hours. After completion of thereaction, the reaction mixture was cooled to room temperature andacidified with 6N hydrochloric acid. The aqueous layer was washed withethyl acetate and made basic with an aqueous sodium hydroxide solution,and the desired compound was extracted three times with ethyl acetate.The combined organic layer was washed with saturated aqueous sodiumchloride solution, dried over anhydrous sodium sulfate, and thendistilled under reduced pressure to remove the solvent, whereby 0.47 gof N-isopropyl-2-methylthioethylamine was obtained (yield: 70%).

¹H-NMR (δ value, ppm/CDCl₃); 1.07 (d, 6H), 1.52 (br, 1H), 2.10 (s, 3H),2.66 (t, 2H), 2.80 (t, 2H), 2.82 (m, 1H).

Example 2

Production of 2-Methyl-1-phenylthio-2-propylamine

In the same manner as in Example 1-1, 2-amino-2-methylpropylhydrogensulfate was quantitatively obtained by using2-amino-2-methyl-1-propanol as a starting material.

In 5 ml of water was dissolved 0.20 g (5 mmol) of sodium hydroxide,followed by adding thereto 0.85 g (5 mmol) of 2-amino-2-methylpropylhydrogensulfate and 0.66 g (6 mmol) of thiophenol, and the resultingmixture was stirred at 80° C. for 8 hours. After completion of thereaction, the reaction mixture was cooled to room temperature andacidified with 6N hydrochloric acid. The aqueous layer was washed withethyl acetate and made basic with an aqueous sodium hydroxide solution,and the desired compound was extracted three times with ethyl acetate.The combined organic layer was washed with saturated aqueous sodiumchloride solution, dried over anhydrous sodium sulfate, and thendistilled under reduced pressure to remove the solvent, whereby 0.52 gof 2-methyl-1-phenylthio-2-propylamine was obtained (yield: 57%).

¹H-NMR (δ value, ppm/CDCl₃); 1.20 (s, 6H), 1.42 (br, 2H), 3.03 (s, 2H),7.16 (t, 1H), 7.28 (dd, 2H), 7.40 (dd, 2H).

Example 3

Production of 2-Methyl-1-methylthio-2-propylamine

In the same manner as in Example 1-1, 2-amino-2-methylpropylhydrogensulfate was quantitatively obtained by using2-amino-2-methyl-1-propanol as a starting material. This2-amino-2-methylpropyl hydrogensulfate was used in the followingreaction in the form of a toluene suspension without isolation.

The obtained suspension of 2-amino-2-methylpropyl hydrogensulfate (in anamount corresponding to 5 mmol) in toluene was ice-cooled, and a mixedsolution of 0.24 g (6 mmol) of sodium hydroxide and 5 ml of water wasadded dropwise thereto. Then, 3.5 g (7.5 mmol) of methylmercaptan sodiumsalt (15% aqueous solution) was added thereto and stirred at 80° C. for2 hours. After completion of the reaction, the reaction mixture wascooled to room temperature and acidified with 6N hydrochloric acid. Theaqueous layer was washed with methyl t-butyl ether (MTBE) and made basicwith an aqueous sodium hydroxide solution, and the desired compound wasextracted three times with MTBE. The combined organic layer was washedwith saturated aqueous sodium chloride solution, dried over anhydroussodium sulfate, and then distilled under reduced pressure to remove thesolvent, whereby 0.48 g of 2-methyl-1-methylthio-2-propylamine wasobtained (yield: 81%).

¹H-NMR (δ value, ppm/CDCl₃); 1.17 (s, 6H), 1.43 (br, 2H), 2.17 (s, 3H),2.56 (s, 2H).

Example 4

Production of 2-Methyl-1-n-octylthio-2-propylamine

In a mixed solvent of 10 ml of water and 10 ml of ethanol was suspended1.38 g (10 mmol) of potassium carbonate. To the suspension were added0.85 g (5 mmol) of 2-amino-2-methylpropyl hydrogensulfate and 0.73 g (5mmol) of 1-octanethiol, and the resulting mixture was gently refluxedfor 8 hours. After completion of the reaction, the reaction mixture wascooled to room temperature and the desired compound was extracted threetimes with ethyl acetate. The combined organic layer was washed withsaturated aqueous sodium chloride solution, dried over anhydrous sodiumsulfate, and then distilled under reduced pressure to remove thesolvent, whereby 1.08 g of 2-methyl-1-n-octylthio-2-propylamine wasobtained. The purity was measured in terms of area percentage by gaschromatography and found to be 91%.

Yield: 100%. ¹H-NMR (δ value, ppm/CDCl₃); 0.87 (t, 3H), 1.16 (s, 1H),1.20-1.60 (m, 14H), 2.54 (t, 2H), 2.57 (s, 2H).

Example 5

Production of 2-Methyl-1-n-octylthio-2-propylamine

2-Methyl-1-n-octylthio-2-propylamine was obtained (yield: 1.06 g) bycarrying out the same reaction as in Example 4 except for changing theamount of potassium carbonate to 0.69 g (5 mmol). The purity wasmeasured in terms of area percentage by gas chromatography and found tobe 84%.

Example 6

Production of 2-Methyl-1-(2-pyridylthio)-2-propylamine

2-Methyl-1-(2-pyridylthio)-2-propylamine was obtained (yield: 83%) bycarrying out the same reaction as in Example 4 except for using2-pyridinethiol as a starting mercaptan.

¹H-NMR (δ value, ppm/CDCl₃); 1.20 (s, 6H), 1.52 (br, 2H), 3.35 (s, 2H),6.96 (m, 1H), 7.21 (d, 1H), 7.44 (ddd, 1H), 8.38 (d, 1H).

The following compounds were produced in the same manner as in Example4:

1-(4-t-Butylphenylthio)-2-methyl-2-propylamine (Yield: 69%)

¹H-NMR (δ value, ppm/CDCl₃); 1.21 (s, 6H), 1.29 (s, 9H), 1.86 (br, 2H),3.03 (s, 2H), 7.30-7.35 (m, 4H).

1-(4-Chlorophenylthio)-2-methyl-2-propylamine (Yield: 57%)

¹H-NMR (δ value, ppm/CDCl₃); 1.21 (s, 6H), 1.84 (br, 2H), 3.02 (s, 2H),7.20-7.28 (m, 2H), 7.29-7.35 (m, 2H).

2-Methyl-1-(2-naphthylthio)-2-propylamine (Yield: 45%)

¹H-NMR (δ value, ppm/CDCl₃); 1.24 (s, 6H), 1.55 (br, 2H), 3.14 (s, 2H),7.38-7.50 (m, 3H), 7.70-7.82 (m, 4H).

1-(4-Chlorobenzylthio)-2-methyl-2-propylamine (Yield: 47%)

¹H-NMR (δ value, ppm/CDCl₃); 1.14 (s, 6H), 1.54 (br, 2H), 2.48 (s, 2H),3.71 (s, 2H), 7.21-7.31 (m, 4H).

1-Ethylthio-2-methyl-2-propylamine (Yield: 72%)

¹H-NMR (δ value, ppm/CDCl₃); 1.17 (s, 6H), 1.25 (dt, 3H), 1.60-1.70 (br,2H), 2.52-2.60 (m, 4H).

2-Methyl-1-n-propylthio-2-propylamine (Yield: 74%)

¹H-NMR (δ value, ppm/CDCl₃); 0.97 (t, 3H), 1.16 (s, 6H), 1.60 (m, 2H),1.72 (br, 2H), 2.52 (t, 2H), 2.56 (s, 2H).

2-Methyl-1-i-propylthio-2-propylamine (Yield: 68%)

¹H-NMR (δ value, ppm/CDCl₃); 1.16 (s, 6H), 1.21-1.31 (m, 6H), 1.69 (br,2H), 2.57 (s, 2H), 2.80-2.92 (m, 1H).

1-t-Butylthio-2-methyl-2-propylamine (Yield: 61%)

¹H-NMR (δ value, ppm/CDCl₃); 1.17 (s, 6H), 1.31 (s, 9H), 1.62 (br, 2H),2.57 (s, 2H).

1-Methylthiomethyl-1-cyclopentylamine (Yield: 32%)

¹H-NMR (δ value, ppm/CDCl₃); 1.45-1.85 (m, 10H), 2.18 (s, 3H), 2.70 (s,2H).

N,N-Dimethyl-2-methylthioethylamine (Yield: 83%)

¹H-NMR (δ value, ppm/CDCl₃); 2.13 (s, 3H), 2.26 (s, 6H), 2.48-2.65 (m,4H).

1-Methylthio-2-propylamine (Yield: 68%)

¹H-NMR (δ value, ppm/CDCl₃); 1.15 (d, 3H), 1.49 (br, 2H), 2.10 (s, 3H),2.36 (dd, 1H), 2.58 (dd, 1H), 3.00-3.12 (m, 1H).

2-Methylthio-N-phenylethylamine (Yield: 41%)

¹H-NMR (δ value, ppm/CDCl₃); 2.12 (s, 3H), 2.78 (t, 2H), 3.34 (t, 2H),4.09 (br, 1H), 6.63 (dd, 2H), 6.73 (t, 1H), 7.19 (dd, 2H).

1-(2-Methylthioethyl)piperidine (Yield: 68%)

¹H-NMR (δ value, ppm/CDCl₃); 1.44 (br, 2H), 1.59 (br, 4H), 2.13 (s, 3H),2.42 (br, 4H), 2.52-2.58 (m, 2H), 2.61-2.67 (m, 2H).

2-Methyl-1-(pyridine-N-oxide-2-ylthio)-2-propylamine (Yield: 60%)

¹H-NMR (δ value, ppm/CDCl₃); 1.28 (d, 3H), 1.8-2.0 (br, 2H), 2.83 (dd,1H), 3.00 (dd, 1H), 3.28 (m, 1H), 7.05 (dt, 1H), 7.16-7.32 (m, 2H), 8.26(d, 1H).

2-methyl-1-(3-pyridylthio)-2-propylamine (Yield: 67%)

H-NMR (δ value, ppm/CDCl₃); 1.14 (m, 3H), 1.7-1.9 (br, 2H), 2.85 (m,1H), 2.94-3.10 (m, 2H), 7.19 (dd, 1H), 7.64 (d, 1H), 8.40 (d, 1H), 8.56(s, 1H).

2-Methyl-1-(4-pyridylthio)-2-propylamine (Yield: 65%)

¹H-NMR (δ value, ppm/CDCl₃); 1.17 (d, 3H), 1.71 (bs, 2H), 3.03 (dd, 1H),3.16 (m, 1H), 3.34 (dd, 1H), 6.95 (t, 1H), 7.16 (d, 1H), 7.41 (dt, 1H),8.36 (d, 1H).

2-Methyl-1-(1H-1,2,4-triazol-3-ylthio)-2-propylamine (Yield: 40%)

¹H-NMR (δ value, ppm/CDCl₃); 1.24 (d, 3H), 2.96 (dd, 1H), 3.22 (dd, 1H),3.36 (m, 1H), 7.99 (s, 1H).

3-Hydroxy-2-methyl-1-methylthio-2-propylamine (Yield: 54%)

¹H-NMR (δ value, ppm/CDCl₃); 1.12 (s, 3H), 2.16 (s, 3H), 2.28 (br, 2H),2.61 (dd, 2H), 3.39 (dd, 2H).

1-Ethylthio-3-hydroxy-2-methyl-2-propylamine (Yield: 40%)

¹H-NMR (δ value, ppm/CDCl₃); 1.13 (s, 3H), 1.26 (t, 3H), 2.58 (dd, 2H),2.64 (dd, 2H), 3.39 (dd, 2H).

1-(t-Butylphenylthio)-3-hydroxy-2-methyl-2-propylamine (Yield: 30%)

¹H-NMR (δ value, ppm/CDCl₃) 1.17 (s, 9H), 1.28 (s, 3H), 2.11 (br, 2H),3.04 (dd, 2H), 3.39 (dd, 2H), 7.26-7.35 (m, 4H).

1-(2-Thienylthio)-2-propylamine (Yield: 78%)

¹H-NMR (δ value, ppm/CDCl₃); 1.14 (d, 3H), 2.61 (dd, 1H), 2.90 (dd, 1H),3.05 (m, 1H), 6.97 (dd, 1H), 7.14 (dd, 1H), 7.34 (dd, 1H).

1-Ethylthio-2-propylamine (Yield: 72%)

¹H-NMR (δ value, ppm/CDCl₃); 1.14 (d, 3H), 1.25 (t, 3H), 1.51 (br, 2H),2.36 (dd, 1H), 2.54 (q, 2H), 2.63 (dd, 1H), 3.03 (m, 1H).

Reference Example 1

Production ofN¹-(4-Heptafluoroisopropyl-2-methylphenyl)-N²-(1-methyl-2-methylthioethyl)-3-methylsulfonylphthalamide(Hereinafter Referred to as “Reference Compound 1”) andN¹-(4-Heptafluoroisopropyl-2-methylphenyl)-N²-(1-methyl-2-methylthioethyl)-6-methylsulfonylphthalamide(Hereinafter Referred to as “Reference Compound 2”)

In 10 ml of dioxane was dissolved 0.63 g ofN-(4-heptafluoroisopropyl-2-methylphenyl)-3-methylsulfonylphthalimide,followed by adding thereto 0.25 g of 1-methylthio-2-propylamine and 0.01g of acetic acid, and the reaction was carried out with heating underreflux for 3 hours. After completion of the reaction, the solvent wasdistilled off under reduced pressure and the resulting residue waspurified by silica gel column chromatography using a 1:1 mixed solventof hexane and ethyl acetate as an eluent, to obtain 0.42 g of thedesired compound (reference compound 1) having an Rf value of 0.5 to 0.7and 0.18 g of the desired compound (reference compound 2) having an Rfvalue of 0.2 to 0.3.

Physical Property:

reference compound 1 m.p. 205-206° C. (Yield: 55%)

reference compound 2 m.p. 210-212° C. (Yield: 24%)

Reference Example 2

Insecticidal Effect on Diamondback Moth (Plutella xylostella)

Adult diamondback moths were released and allowed to oviposit on aChinese cabbage seedling. Two days after the release, the seedlinghaving eggs deposited thereon was immersed for about 30 seconds in aliquid chemical prepared by diluting a preparation containing each ofthe reference compounds as an active ingredient to adjust theconcentration to 500 ppm. After air-drying, the seedling was allowed tostand in a room thermostated at 25° C. Six days after the immersion inthe liquid chemical, the hatched insects were counted and the mortalitywas calculated according to the following equation. The test was carriedout with three replications.${{Corrected}\quad {mortality}\quad (\%)} = {\frac{\begin{pmatrix}{{Number}\quad {of}} \\{{hatched}\quad {insects}} \\{{in}\quad {untreated}} \\{group}\end{pmatrix} - \begin{pmatrix}{{Number}\quad {of}} \\{{hatched}\quad {insects}} \\{{in}\quad {treated}} \\{group}\end{pmatrix}}{\begin{pmatrix}{{Number}\quad {of}\quad {hatched}\quad {insects}} \\{{in}\quad {untreated}\quad {group}}\end{pmatrix}} \times 100}$

As a result, the reference compounds 1 and 2 were found to have amortality of 100%.

Reference Example 3

Insecticidal Effect on Common Cutworm (Spodoptera litura)

A piece of cabbage leaf (cultivar: Shikidori) was immersed for about 30seconds in a liquid chemical prepared by diluting a preparationcontaining each of the reference compounds as an active ingredient toadjust the concentration to 500 ppm. After air-drying, the piece wasplaced in a plastic Petri dish with a diameter of 9 cm whose bottom hadbeen covered with a wetted filter paper. The piece was inoculated withthird-instar larvae of common cutworm and the Petri dish was allowed tostand in a room thermostated at 25° C. and having a relative humidity of70%. Eight days after the inoculation, the dead and alive were countedand the mortality was calculated according to the following equation.The test was carried out with three replications of 10 insects.${{Corrected}\quad {mortality}\quad (\%)} = {\frac{\begin{pmatrix}{{Number}\quad {of}} \\{{surviving}\quad {insects}} \\{{in}\quad {untreated}} \\{group}\end{pmatrix} - \begin{pmatrix}{{Number}\quad {of}} \\{{surviving}\quad {insects}} \\{{in}\quad {treated}} \\{group}\end{pmatrix}}{\begin{pmatrix}{{Number}\quad {of}\quad {surviving}\quad {insects}} \\{{in}\quad {untreated}\quad {group}}\end{pmatrix}} \times 100}$

As a result, the reference compound 1 was found to have a mortality of100%.

What is claimed is:
 1. A process for producing a thioalkylaminerepresented by formula (I):

(wherein R₁, R₂, R₃, R₄, R₅, R₆ and R are as defined below),characterized by reacting sulfuric acid with an amino alcoholrepresented by formula (II):

(wherein each of R₁ and R₂, which may be the same or different, is ahydrogen atom; a (C₁-C₄)alkyl group; a (C₃-C₈)cycloalkyl group; a(C₃-C₈)cycloalkyl(C₁-C₄)alkyl group; a hydroxy(C₁-C₄)alkyl group; aphenyl group; a substituted phenyl group having 1 to 5 substituentswhich may be the same or different and each of the substituents isselected from a halogen atom, a cyano group, a nitro group, a(C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a (C₃-C₈)cycloalkyl group,a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthiogroup, a halo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, a (C₁-C₄)alkylsulfonyl group, ahalo(C₁-C₄)alkylsulfonyl group, a carboxyl group, a(C₁-C₄)alkoxycarbonyl group, a (C₁-C₄)alkoxy(C₁-C₄)alkyl group,R₇—C(═O)— (wherein R₇ is a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group,a phenyl group or a phenoxy group), an amino group, and a substitutedamino group having one or two substituents which may be the same ordifferent and are selected from (C₁-C₄)alkyl groups; a substitutedphenyl group having as the substituent a (C₃-C₄)alkylene group or a(C₁-C₂)alkylenedioxy group, which forms a ring together with a pair ofadjacent carbon atoms in the benzene ring; a phenyl(C₁-C₄)alkyl group;or a substituted phenyl(C₁-C₄)alkyl group having on the ring 1 to 5substituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a cyano group, a nitrogroup, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; R₁ andR₂ may form a (C₂-C₅)alkylene group by binding to each other; R₁ and R₃or R₅ may form a (C₃-C₅)alkylene group by binding to each other, each ofR₃ and R₄, which may be the same or different, is a hydrogen atom or a(C₁-C₄)alkyl group; R₃ and R₄ may form a (C₄-C₆)alkylene group bybinding to each other; R₃ and R₅ may form a (C₂-C₄)alkylene group bybinding to each other, each of R₅ and R₆, which may be the same ordifferent, is a hydrogen atom; a (C₁-C₄)alkyl group; a phenyl group; asubstituted phenyl group having 1 to 5 substituents which may be thesame or different and each of the substituents is selected from ahalogen atom, a cyano group, a nitro group, a (C₁-C₄)alkyl group, ahalo(C₁-C₄)alkyl group, a (C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxygroup, a halo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthio group, ahalo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, a (C₁-C₄)alkylsulfonyl group and ahalo(C₁-C₄)alkylsulfonyl group; a phenyl(C₁-C₄)alkyl group; or asubstituted phenyl(C₁-C₄)alkyl group having on the ring 1 to 5substituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a cyano group, a nitrogroup, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; and R₅and R₆ may form a (C₄-C₆)alkylene group by binding to each other) toobtain a sulfate ester represented by formula (III):

(wherein R¹, R₂, R₃, R₄, R₅ and R₆ are as defined above), and reactingthe sulfate ester, after or without isolation, with a mercaptanrepresented by formula (IV): RSM  (IV) (wherein R is a (C₁-C₁₂)alkylgroup; a (C₃-C₈)cycloalkyl group; a (C₃-C₈)cycloalkyl(C₁-C₄)alkyl group;a phenyl group; a substituted phenyl group having 1 to 5 substituentswhich may be the same or different and each of the substituents isselected from a halogen atom, a (C₁-C₆)alkyl group, a halo(C₁-C₃)alkylgroup, a (C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group and ahalo(C₁-C₄)alkoxy group; a phenyl(C₁-C₄)alkyl group; a substitutedphenyl(C₁-C₄)alkyl group having on the ring 1 to 5 substituents whichmay be the same or different and each of the substituents is selectedfrom a halogen atom and a (C₁-C₄)alkyl group; a naphthyl group; anaromatic heterocyclic group; or a substituted aromatic heterocyclicgroup having one or more substituents which may be the same or differentand each of the substituents is selected from a halogen atom, a(C₁-C₄)alkyl group, a (C₁-C₄)alkoxy group, a phenyl group and asubstituted phenyl group having 1 to 5 substituents which may be thesame or different and each of the substituents is selected from ahalogen atom and a (C₁-C₄)alkyl group, and M is a hydrogen atom, anammonium group or an alkali metal atom).
 2. A process for producing athioalkylamine represented by formula (I):

(wherein R₁, R₂, R₃, R₄, R₅, R₆ and R are as defined below),characterized by reacting a sulfate ester represented by formula (III):

(wherein each of R₁ and R₂, which may be the same or different, is ahydrogen atom; a (C₁-C₄)alkyl group; a (C₃-C₈)cycloalkyl group; a(C₃-C₈)cycloalkyl(C₁-C₄)alkyl group; a hydroxy(C₁-C₄)alkyl group; aphenyl group; a substituted phenyl group having 1 to 5 substituentswhich may be the same or different and each of the substituents isselected from a halogen atom, a cyano group, a nitro group, a(C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a (C₃-C₈)cycloalkyl group,a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthiogroup, a halo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, (C₁-C₄)alkylsulfonyl group, ahalo(C₁-C₄)alkylsulfonyl group, a carboxyl group, a(C₁-C₄)alkoxycarbonyl group, a (C₁-C₄)alkoxy(C₁-C₄)alkyl group,R₇—C(═O)— (wherein R₇ is a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group,a phenyl group or a phenoxy group), an amino group, and a substitutedamino group having one or two substituents which may be the same ordifferent and are selected from (C₁-C₄)alkyl groups; a substitutedphenyl group having as the substituent a (C₃-C₄)alkylene group or a(C₁-C₂)alkylenedioxy group, which forms a ring together with a pair ofadjacent carbon atoms in the benzene ring; a phenyl(C₁-C₄)alkyl group;or a substituted phenyl(C₁-C₄)alkyl group having on the ring 1 to 5substituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a cyano group, a nitrogroup, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; R₁ andR₂ may form a (C₂-C₅)alkylene group by binding to each other; R₁ and R₃or R₅ may form a (C₃-C₅)alkylene group by binding to each other, each ofR₃ and R₄, which may be the same or different, is a hydrogen atom or a(C₁-C₄)alkyl group; R₃ and R₄ may form a (C₄-C₆)alkylene group bybinding to each other; R₃ and R₅ may form a (C₂-C₄)alkylene group bybinding to each other, each of R₅ and R₆, which may be the same ordifferent, is a hydrogen atom; a (C₁-C₄)alkyl group; a phenyl group; asubstituted phenyl group having 1 to 5 substituents which may be thesame or different and each of the substituents is selected from ahalogen atom, a cyano group, a nitro group, a (C₁-C₄)alkyl group, ahalo(C₁-C₄)alkyl group, a (C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxygroup, a halo(C₁-C₄)alkoxy group, a (C₁-C₄)alkylthio group, ahalo(C₁-C₄)alkylthio group, a (C₁-C₄)alkylsulfinyl group, ahalo(C₁-C₄)alkylsulfinyl group, a (C₁-C₄)alkylsulfonyl group and ahalo(C₁-C₄)alkylsulfonyl group; a phenyl(C₁-C₄)alkyl group; or asubstituted phenyl(C₁-C₄)alkyl group having on the ring 1 to 5substituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a cyano group, a nitrogroup, a (C₁-C₄)alkyl group, a halo(C₁-C₄)alkyl group, a(C₃-C₈)cycloalkyl group, a (C₁-C₄)alkoxy group, a halo(C₁-C₄)alkoxygroup, a (C₁-C₄)alkylthio group, a halo(C₁-C₄)alkylthio group, a(C₁-C₄)alkylsulfinyl group, a halo(C₁-C₄)alkylsulfinyl group, a(C₁-C₄)alkylsulfonyl group and a halo(C₁-C₄)alkylsulfonyl group; and R₅and R₆ may form a (C₄-C₆)alkylene group by binding to each other) with amercaptan represented by formula (IV): RSM  (IV) (wherein R is a(C₁-C₁₂)alkyl group; a (C₃-C₈)cycloalkyl group; a(C₃-C₈)cycloalkyl(C₁-C₄)alkyl group; a phenyl group; a substitutedphenyl group having 1 to 5 substituents which may be the same ordifferent and each of the substituents is selected from a halogen atom,a (C₁-C₆)alkyl group, a halo(C₁-C₃)alkyl group, a (C₃-C₈)cycloalkylgroup, a (C₁-C₄)alkoxy group and a halo(C₁-C₄)alkoxy group; aphenyl(C₁-C₄)alkyl group; a substituted phenyl(C₁-C₄)alkyl group havingon the ring 1 to 5 substituents which may be the same or different andeach of the substituents is selected from a halogen atom and a(C₁-C₄)alkyl group; a naphthyl group; an aromatic heterocyclic group; ora substituted aromatic heterocyclic group having one or moresubstituents which may be the same or different and each of thesubstituents is selected from a halogen atom, a (C₁-C₄)alkyl group, a(C₁-C₄)alkoxy group, a phenyl group and a substituted phenyl grouphaving 1 to 5 substituents which may be the same or different and eachof the substituents is selected from a halogen atoms and a (C₁-C₄)alkylgroup, and M is a hydrogen atom, an ammonium group or an alkali metalatom) in the presence of a base.